Blood Res.  2016 Dec;51(4):261-267. 10.5045/br.2016.51.4.261.

Effect of short-term, high-dose methylprednisolone on oxidative stress in children with acute immune thrombocytopenia

• Cura M
• Koç A
• Aksoy N
• Özdemir Z

• KMID: 2364317
• DOI: http://doi.org/10.5045/br.2016.51.4.261

Abstract

BACKGROUND
Immune thrombocytopenia (ITP) is the most common cause of acquired childhood thrombocytopenia and is characterized by increased immune-mediated destruction of circulating thrombocytes. Oxidative damage may be involved in ITP pathogenesis; paraoxonase (PON) and arylesterase (ARE) enzymes are closely associated with the cellular antioxidant system. We investigated the effect of short-term high-dose methylprednisolone (HDMP) treatment on the total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and PON and ARE enzymatic activity in children with acute ITP.
METHODS
Thirty children with acute ITP constituted the study group and 30 healthy children constituted the control group. Children with acute ITP were treated with HDMP: 30 mg/kg for 3 days, then 20 mg/kg for 4 days. The TOS, TAC, OSI, PON, and ARE levels were determined before and after 7 days of HDMP treatment.
RESULTS
The TAC level (P<0.001), and PON (P<0.001) and ARE (P=0.001) activities were lower and the TOS (P=0.003) and OSI (P<0.001) levels were higher in children with acute ITP than those in healthy children in the control group. We also observed statistically significant increases in the TAC (P<0.01), PON (P<0.001) and ARE levels (P=0.001) and decreases in the TOS (P<0.05) and OSI levels (P<0.05) with 7 days of HDMP treatment compared to their values before treatment.
CONCLUSION
Our study demonstrated increased oxidative stress (OSI and TOC) and decreased antioxidant capacity (TAC), PON, and ARE in ITP patients and that steroid treatment could be effective in reducing the oxidative stress.

Keyword

ITP; Paraoxonase; Arylesterase; Child; Methylprednisolone

MeSH Terms

Aryldialkylphosphatase
Blood Platelets
Child*
Humans
Methylprednisolone*
Oxidative Stress*
Purpura, Thrombocytopenic, Idiopathic*
Thrombocytopenia
Aryldialkylphosphatase
Methylprednisolone

Figure

• 

  Fig. 1 The possible role of oxidative stress and paraoxonase (PON)/arylesterase (ARE) in the pathogenesis of acute immune thrombocytopenia. Following a triggering event such as infection or inflammation, antibody-coated platelets are destroyed by macrophages in the spleen and liver. The released foreign peptide fragments are presented to the T- and B-lymphocytes. While antibody synthesis continues with the stimulation of the B-lymphocytes, the peripheral thrombocyte destruction continues due to the cytotoxic T-lymphocytes activation. During the destruction of platelets in the reticuloendothelial system and the periphery, reactive oxygen species (ROS) are produced. Increasing ROS levels induces a decrease in the total antioxidant capacity (TAC) and an increase in the total oxidant status (TOS). As a result of this increased oxidative stress, deoxyribonucleic acid (DNA), protein, and lipid peroxidation ensues. Lipid peroxidation leads to formation of oxidized low-density lipoproteins (LDL). The released oxidized phospholipids and cholesterol esters interact with the free sulfhydryl groups of paraoxonase (PON), and inhibit the PON and arylesterase (ARE) activities. In addition, the PON activity is also reduced due to systemic inflammation. As a result, dysfunctional high-density lipoproteins (HDL) with impaired anti-atherogenic effects are produced. This impaired anti-atherogenic effect of HDL may increase the tendency to atherosclerosis.

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  Fig. 2 Boxplot graph of TAC levels before and 7 days of after treatment in the ITP group and control group.Abbreviations: TAC, total antioxidant capacity; ITP, Immune thrombocytopenia.

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  Fig. 3 Boxplot graph of OSI levels before and 7 days of after treatment in the ITP group and control group.Abbreviations: OSI, oxidative stress index; ITP, Immune thrombocytopenia.

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  Fig. 4 Boxplot graph of PON levels before and 7 days of after treatment in the ITP group and control group.Abbreviations: PON, paraoxonase; ITP, Immune thrombocytopenia.

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  Fig. 5 Boxplot graph of ARE levels before and 7 days of after treatment in the ITP group and control group.Abbreviations: ARE, arylesterase; ITP, Immune thrombocytopenia.

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